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One multiple-mutant strain (Omicron) with surprisingly\ninfective activity outburst, and affected the biological activities of current\ndrugs and vaccines, making the epidemic significantly difficult to prevent and\ncontrol, and seriously threaten health around the world. Importunately\nexploration of mutant characteristics for novel coronavirus Omicron can supply\nstrong theoretical guidance for learning binding mechanism of mutant viruses.\nWhat\u2019s more, full acknowledgement of key mutated-residues on Omicron strain can\nprovide new methodology of the novel pathogenic mechanism to human ACE2\nreceptor, as well as the subsequent vaccine development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this research, 3D structures of 32 single-point mutations\nof 2019-nCov were firstly constructed, and 32-sites multiple-mutant Omicron\nwere finally obtained based one the wild-type virus by homology modeling method.\nOne total number of 33 2019-nCov\/ACE2 complex systems were acquired by\nprotein-protein docking, and optimized by using preliminary molecular dynamic\nsimulations. Binding free energies between each 2019-nCov mutation system and\nhuman ACE2 receptor were calculated, and corresponding binding patterns\nespecially the regions adjacent to mutation site were analyzed. The results\nindicated that one total number of 6 mutated sites on the Omicron strain played\ncrucial role in improving binding capacities from 2019-nCov to ACE2 protein.\nSubsequently, we performed long-term molecular dynamic simulations and\nprotein-protein binding energy analysis for the selected 6 mutations. 3\ninfected individuals, the mutants T478K, Q493R and G496S with lower binding\nenergies -66.36, -67.98 and -67.09 kcal\/mol also presents the high infectivity.\nThese findings indicated that the 3 mutations T478K, Q493R and G496S play the\ncrucial roles in enhancing binding affinity of Omicron to human ACE2 protein.\nAll these results illuminate important theoretical guidance for future virus\ndetection of the Omicron epidemic, drug research and vaccine development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00894-023-05536-1","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T07:02:35Z","timestamp":1682319755000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Binding affinity improvement analysis of multiple-mutant Omicron on 2019-nCov to human ACE2 by in silico predictions"],"prefix":"10.1007","volume":"29","author":[{"given":"Bo","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8673-6267","authenticated-orcid":false,"given":"Jindan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxiang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"5536_CR1","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/S2213-2600(20)30076-X","volume":"8","author":"Z Xu","year":"2020","unstructured":"Xu Z, Shi L, Wang YJ, Zhang JY, Huang L (2020) Pathological findings of COVID-19 associated with acute respiratory distress syndrome. 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